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Volume 501 Issue 7466, 12 September 2013

Juvenile harvest mice engaged in social play. The neural mechanisms underlying the encoding of social reward have remained unknown, despite the need for reinforcement of adaptive social interactions in order to keep such behaviours persistent throughout evolution. Here, Robert Malenka and colleagues report that, in the mouse nucleus accumbens core, the peptide hormone oxytocin is required both for social reinforcement and a form of presynaptic long-term depression of excitatory transmission onto medium spiny neurons. This social reinforcement signal could be disrupted if oxytocin receptors were specifically deleted from inputs arriving from the dorsal raphe nucleus, the major source of serotonin in the brain, or by blocking serotonergic receptors in the nucleus accumbens. Such coordinated activity between oxytocin and serotonin systems provides a possible mechanism for encoding social reinforcement and offers targets for studying further the neural mechanisms of social dysfunction. Cover: Jean-Louis Klein & Marie-Luce Hubert.

Editorial

  • Four US studies are set to explore how genomic data can best help healthy and ill newborns. They must also settle some questions of ethics.

    Editorial

    Advertisement

  • The grey wolf is at risk of losing its endangered status under US law.

    Editorial
  • Don’t treat a memoir as anything other than one person’s interpretation of events.

    Editorial
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World View

  • The effects of federal budget cuts provide an opportunity to revisit the funding structure of the National Institutes of Health, says Frederick Grinnell.

    • Frederick Grinnell
    World View
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Research Highlights

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Seven Days

  • The week in science: Labour strike ends at ALMA observatory, NASA homes in on next Mars landing site, and Taiwan court clears environmental engineer of libel.

    Seven Days
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News

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Correction

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News Feature

  • To track the fate of threatened species, a young scientist must follow the jungle path of a herpetologist who led a secret double life.

    • Brendan Borrell
    News Feature
  • Physicists have spent a century puzzling over the paradoxes of quantum theory. Now a few of them are trying to reinvent it.

    • Philip Ball
    News Feature
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Comment

  • European collaboration is not far behind that in the United States, but there is still work to be done on cross-border funding and financial inequalities, says Paul Boyle.

    • Paul Boyle
    Comment
  • It is time to probe whether the trend for patient and public involvement in medical research is beneficial, say Sophie Petit-Zeman and Louise Locock.

    • Sophie Petit-Zeman
    • Louise Locock
    Comment
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Books & Arts

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Correspondence

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Obituary

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News & Views

  • A mathematical model of gun ownership has been developed that clarifies the debate on gun control and tentatively suggests that firearms restrictions may reduce the homicide rate.

    • Adeline Lo
    • James H. Fowler
    News & Views
  • A genome-wide screen of developing mouse embryos, performed using RNA-interference techniques, finds new suspects in skin cancer. But some factors seem to have opposing roles in cancer and normal-tissue maintenance. See Article p.185

    • Pawel J. Schweiger
    • Kim B. Jensen
    News & Views
  • A spectroscopic technique has been demonstrated that uses stimulated emission to enhance weak X-ray signals for fundamental studies in materials science. See Letter p.191

    • Ernst Fill
    News & Views
  • Host-cell detection of lipopolysaccharide in the outer membrane of Gram-negative bacteria was thought to be restricted to the cell-surface receptor TLR4. It emerges that lipopolysaccharide can also be sensed in the cytoplasm.

    • Vijay A. K. Rathinam
    • Katherine A. Fitzgerald
    News & Views
  • Fingerprints of sulphur isotopes in rocks from the ridge beneath the Atlantic Ocean suggest that a substantial fraction of sulphur at Earth's surface is left over from the formation of the planet's core. See Letter p.208

    • Nicolas Dauphas
    News & Views
  • Cellular cross-talk, enzymatic catalysis and regulation of gene expression all depend on molecular recognition. A method that allows the design of proteins with desired recognition sites could thus be revolutionary. See Letter p.212

    • Giovanna Ghirlanda
    News & Views
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Article

  • In male mice oxytocin acts as a social reinforcement signal within the nucleus accumbens (NAc) core, where it elicits a presynaptically expressed long-term depression (LTD) of excitatory synaptic transmission in medium spiny neurons; deletion of oxytocin receptors from the dorsal raphe nucleus, which provides serotonergic innervation of the NAc, and blockade of NAc serotonin 1B receptors both prevent oxytocin-induced LTD and social reward.

    • Gül Dölen
    • Ayeh Darvishzadeh
    • Robert C. Malenka
    Article
  • Here, the first genome-wide in vivo RNA interference screens in a mammalian animal model are reported: genes involved in normal and abnormal epithelial cell growth are studied in developing skin tissue in mouse embryos, and among the findings, β-catenin is shown to act as an antagonist to normal epithelial cell growth as well as promoting oncogene-driven growth.

    • Slobodan Beronja
    • Peter Janki
    • Elaine Fuchs
    Article
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Letter

  • Resonant inelastic X-ray scattering requires very high photon densities to detect the relatively weak signals of interest, but here it is demonstrated that inducing stimulated X-ray emission from crystalline silicon can increase the signal level by several orders of magnitude and reduces sample damage.

    • M. Beye
    • S. Schreck
    • A. Föhlisch
    Letter
  • Tertiary alcohols are displaced with a nitrogen nucleophile with stereoinversion and with high selectivity over less substituted alcohols, providing complementarity to the SN2 reaction and efficient access to nitrogenous marine terpenoids.

    • Sergey V. Pronin
    • Christopher A. Reiher
    • Ryan A. Shenvi
    Letter
  • Reconstructed changes in North Atlantic nitrogen fixation over the past 160,000 years have a 23,000-year cycle that is interpreted to result from precession-paced changes in the supply of phosphorus to surface waters by equatorial Atlantic upwelling.

    • Marietta Straub
    • Daniel M. Sigman
    • Gerald H. Haug
    Letter
  • Holocene aquifers are the source of much arsenic poisoning in south and southeast Asia, whereas Pleistocene aquifers are mostly safe; here the delayed arsenic contamination of a Pleistocene aquifer is described and modelled.

    • Alexander van Geen
    • Benjamín C. Bostick
    • Michael Berg
    Letter
  • Earth’s mantle is shown to display heterogeneous sulphur isotope ratios, with a depleted end-member that is not chondritic as has been thought; the mantle’s inferred composition can be accounted for by fractionation during core–mantle differentiation.

    • J. Labidi
    • P. Cartigny
    • M. Moreira
    Letter
  • Computational protein design is used to create a protein that binds the steroid digoxigenin (DIG) with high affinity and selectivity; the computational design methods described here should help to enable the development of a new generation of small molecule receptors for synthetic biology, diagnostics and therapeutics.

    • Christine E. Tinberg
    • Sagar D. Khare
    • David Baker
    Letter
  • Exome sequencing has found an excess of de novo mutations in the 4,000 most intolerant genes in patients with two classical epileptic encephalopathies (infantile spasms and Lennox–Gastaut syndrome); among them are multiple de novo mutations in GABRB3 and ALG13.

    • Andrew S. Allen
    • Samuel F. Berkovic
    • Melodie R. Winawer
    Letter
  • Expression of the three transcription factors BLIMP1, PRDM14 and TFAP2C, or of PRDM14 alone, converts epiblast-like cells into primordial germ cell (PGC)-like cells; the transcription-factor-induced PGC-like cells acquire key transcriptome and epigenetic reprogramming in PGCs, and contribute to spermatogenesis and fertile offspring.

    • Fumio Nakaki
    • Katsuhiko Hayashi
    • Mitinori Saitou
    Letter
  • Using 4C technology, higher-order topological features of the pluripotent genome are identified; in pluripotent stem cells, Nanog clusters specifically with other pluripotency genes and this clustering is centred around Nanog-binding sites, suggesting that Nanog helps to shape the three-dimensional structure of the pluripotent genome and thereby contributes to the robustness of the pluripotent state.

    • Elzo de Wit
    • Britta A. M. Bouwman
    • Wouter de Laat
    Letter
  • The mechanism of action of three different allosteric MEK inhibitors that target the MAP kinase pathway is investigated, and their efficacy is shown to be explained by the distinct mechanisms regulating MEK activation in KRAS- versus BRAF-driven tumours; this work provides a rationale for designing more effective cancer therapies for these common genetic subtypes of cancer.

    • Georgia Hatzivassiliou
    • Jacob R. Haling
    • Marcia Belvin
    Letter
  • Colonizing enteric bacteria are shown to inhibit the antimicrobial process of host cell apoptosis through the action of NleB1, a type III secretion system effector with N-acetylglucosamine transferase activity, which can bind and modify eukaryotic death-domain-containing proteins.

    • Jaclyn S. Pearson
    • Cristina Giogha
    • Elizabeth L. Hartland
    Letter
  • Neuropilin-1 (Nrp1) on regulatory T (Treg) cells is shown to interact with semaphorin-4a (Sema4a) to promote a program of Treg-cell stability and survival, in part through PTEN-mediated modulation of Akt signalling; Nrp1-deficient Treg cells can maintain immune homeostasis but fail to suppress in inflammatory sites, such as tumours, providing an attractive immunotherapeutic target for the treatment of cancers.

    • Greg M. Delgoffe
    • Seng-Ryong Woo
    • Dario A. A. Vignali
    Letter
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Retraction

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Corrigendum

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Technology Feature

  • Advances in high-throughput sequencing are accelerating genomics research, but crucial gaps in data remain.

    • Vivien Marx
    Technology Feature
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Feature

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Career Brief

  • NASA starts initiative to study effects of spaceflight.

    Career Brief
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Futures

  • The rhythm of life.

    • William Meikle
    Futures
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